The alpha and beta/gamma subunits of signal-transducing G proteins are maintained in an inactive state by their mutual association in a heterotrimeric complex. Within this assembly, the alpha subunit binds GDP with high affinity, and this interaction is stabilized by beta/gamma. Thus sequestered, neither alpha nor beta/gamma can interact with downstream effectors. Ligand-activated ransmembrane receptors interact with G-protein heterotrimers and induce the dissociation of GDP and exchange of GDP for GTP. Further conformational changes then result in dissociation of alpha/GTP from bg, there by liberating the two activated signal generating molecules. With data sets measured at the A1 and F1 CHESS beamlines from crystals of native heterotrimer and a selenomethionyl derivative, we have determined the crystallographic structure of the G protein heterotrimer G(i)alpha(GDP)/beta1/gamma2 at 2.3 Angstrom resolution. The structure reveals two nonoverlapping regions of contact between alpha and beta, an extended interface between beta and nearly all of gamma,but limited interaction of alpha with gamma. The major alpha/beta interface covers switch II of alpha, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared to alpha-GDP) explain stabilization of the inactive conformation of alpha by beta/gamma. Repeated WD motifs in beta (of which this is the first reported of a large structural family of regulatory proteins) form a circularized seven-fold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade. Data sets have also been mearured from crystals of the free beta1/gamma2 complex, and strucure determination is in progress. Structures of several mutants of the alpha subunits (e.g. G42S and S47N) with unusual catalytic properties have also been revealed with Synchrotron radiation.